Project Abstract The integration of information from different sensory systems is critical for animals to form an accurate perception of their surroundings and to act decisively and rapidly in response to environmental cues. Traditionally, it was assumed that multisensory integration only occurs in higher-order association areas of the brain. However, recent studies have found neurons in early ?unisensory? brain areas, such as the primary olfactory cortex, that respond to multiple sensory modalities, such as odor and taste stimuli. Physiological and behavioral observations suggest that unisensory and multisensory integration engage different underlying computations. Furthermore, the failure of multisensory integration in humans is a common symptom of disorders such as autism and schizophrenia, which combined affect ~70 million people worldwide. Yet, we know very little about how and where multi-sensory integration occurs, how it modifies the response properties of neurons, and the synaptic and cellular mechanisms underlying this integration. The goal of this research is to combine quantitative behavioral analysis and optical neurophysiology in the Drosophila larva to elucidate how multisensory integration occurs both at the behavioral level and in the first olfactory processing center of the larval brain, called the antennal lobe (AL). The larva is an ideal system to study these questions in because it has a small number (~20) of uniquely identifiable, putative multisensory neurons in the AL that respond to odors and tastes. Furthermore, it is possible to non-invasively monitor and manipulate activity in individual neurons of awake larvae while delivering controlled odor and taste stimuli, and to quantify responses of freely behaving larvae while navigating in olfactory and gustatory environments. The first aim will characterize and compare how larval behavioral features are modified while navigating in concurrent olfactory and gustatory gradients versus a single sensory gradient. The second aim will functionally identify neurons in the AL that respond to tastes and odors and characterize the responses of these neurons to unimodal stimuli. The third aim will define the temporal dynamics of integration in multisensory neurons of the AL by delivering odor-taste sequences with varying time delays and concentrations. These experiments will begin to address the question of how multisensory inputs interact to modify sensory processing and give rise to multisensory perception and behavior. Neural mechanisms responsible for olfactory-gustatory integration will likely inform how integration of other sensory systems occurs and may hold true across species.